Project Summary/Abstract Cancer incidence has greatly increased in low- and medium-resource countries as a result of economic and social shifts, which have contributed to an increase in population size and the aging of populations, as well as altered the pattern of exposure to risk factors such as tobacco and alcohol, overweight and obesity, reproductive habits, and occupational agents. Epidemiologic studies conducted in populations in transition in medium-resource countries have stressed the role of such lifestyle factors in determining the rapid change in cancer risk. However, most of these studies were designed as case-control studies, the retrospective design of which provides greater risks of selection and information biases than prospective cohort studies. Cohort studies are better able to take advantage of large exposure and risk contrasts in low- and medium-resource countries to investigate the effects of the transition that is occurring in many of these populations. This approach is helpful for both common cancers and, if large enough populations can be assembled in consortium-based pooled analyses, for rarer and less widely studied neoplasms. We aim to conduct a pooled analysis of cohort studies from Asia to assess the contribution of tobacco, alcohol, and elevated BMI to the etiology of cancer of the small intestine, as the first study in a series on rare cancers. The analysis will also test the hypothesis of heterogeneity in the etiologic factors between the main type of cancer of the small intestine, adenocarcinoma (AC), and other histologic types. The pooled analysis will be conducted among cohorts within the Asia Cohort Consortium (ACC), which was recently established with the goal of promoting collaboration and data pooling among current and future epidemiologic cohort studies in Asia. Our consortium addresses the NCI objective to "expand the capacity of centers, networks, and consortia," and the goal to "create and sustain infrastructures that facilitate research collaboration, serve as platforms for technology development, and provide access to the full range of research resources," as outlined in the NCI Plans and Priorities. We anticipate that the analysis within the ACC will be a major step toward improving understanding of the causes and mechanisms of rare cancers and will enhance the collaboration within the consortium for further pooled analyses. Furthermore, we plan to pool the ACC data with those of other large cohorts from North America and Europe to further increase the statistical power of looking at risk factors of small intestine cancer. PUBLIC HEALTH RELEVANCE: Project Narrative The burden of cancer has greatly increased in low- and medium-resource countries in recent years, as a consequence of the increase in population size, the aging of the population, and changes in pattern of exposure to risk factors, including tobacco smoking, alcohol drinking, overweight and obesity, reproductive habits, and occupational agents. Epidemiologic studies in populations in transition in medium-resource countries will generate evidence on cancer etiology that is relevant also for the United States and other high- income countries, owing to the capacity to assess the effect of broader exposure ranges, especially at the low end of the spectrum (e.g., caloric intake, body mass index). This approach will be helpful both for common cancers and, if large enough populations can be assembled in consortium-based pooled analyses, for rarer and less widely studied neoplasms such as small intestine cancer, as proposed in this research.